The sinoatrial (SA) node is located in the wall of the right atrium near the entrance of the superior vena cava. The specialized cells of the SA node spontaneously depolarize to threshold and generate 70 to 75 heart beats/ min. The "resting" membrane potential, or pacemaker potential, is different from that of neurons, which were discussed in Chapter 3 (Membrane Potential). First of all, this potential is approximately -55 mV, which is less negative than that found in neurons (-70 mV; see Figure 13.2, panel A). Second, pacemaker potential is unstable and slowly depolarizes toward threshold (phase 4). Two important ion currents contribute to this slow depolarization. These cells are inherently leaky to sodium. The resulting influx of Na+ ions occurs through channels that differ from the fast Na+ channels that cause rapid depolarization in other types of excitable cells. Toward the end of phase

Figure 13.2 Cardiac action potentials. Panel A: sinoatrial (SA) node; during phase 4 (the pacemaker potential), the cells of the SA node depolarize toward threshold due to the influx of Na+ and Ca++ ions. The upward swing of the action potential, phase 0, results from the influx of calcium through slow Ca++ channels. Repolarization (phase 3) is due to the efflux of K+ ions. Panel B: ventricular muscle; the resting membrane potential (phase 4) is very negative due to the high permeability of the K+ channels. The upward swing of the action potential (phase 0) results from the rapid influx of sodium through fast Na+ channels. The brief repolarization that occurs during phase 1 is due to the abrupt closure of the channels. The plateau of the action potential, phase 2, results from the influx of calcium through slow Ca++ channels. Finally, repolarization (phase 3) is due to the efflux of K+ ions. The absolute, or effective, refractory period (ARP) persists until the fast Na+ channels return to their resting state (-70 mV). No new action potentials may be generated during this period. This is followed by the relative refractory period (RRP).

Figure 13.2 Cardiac action potentials. Panel A: sinoatrial (SA) node; during phase 4 (the pacemaker potential), the cells of the SA node depolarize toward threshold due to the influx of Na+ and Ca++ ions. The upward swing of the action potential, phase 0, results from the influx of calcium through slow Ca++ channels. Repolarization (phase 3) is due to the efflux of K+ ions. Panel B: ventricular muscle; the resting membrane potential (phase 4) is very negative due to the high permeability of the K+ channels. The upward swing of the action potential (phase 0) results from the rapid influx of sodium through fast Na+ channels. The brief repolarization that occurs during phase 1 is due to the abrupt closure of the channels. The plateau of the action potential, phase 2, results from the influx of calcium through slow Ca++ channels. Finally, repolarization (phase 3) is due to the efflux of K+ ions. The absolute, or effective, refractory period (ARP) persists until the fast Na+ channels return to their resting state (-70 mV). No new action potentials may be generated during this period. This is followed by the relative refractory period (RRP).

Phase 0 begins when the membrane potential reaches threshold (-40 mV). Recall that the upstroke of the action potential in neurons is due to increased permeability of fast Na+ channels, resulting in a steep, rapid depolarization.

However, in the SA node, the action potential develops more slowly because the fast Na+ channels do not play a role. Whenever the membrane potential is less negative than -60 mV for more than a few milliseconds, these channels become inactivated. With a resting membrane potential of -55 mV, this is clearly the case in the SA node. Instead, when the membrane potential reaches threshold in this tissue, many slow Ca++ channels open, resulting in the depolarization phase of the action potential. The slope of this depolarization is less steep than that of neurons.

Phase 3 begins at the peak of the action potential. At this point, the Ca++ channels close and K+ channels open. The resulting efflux of K+ ions causes the repolarization phase of the action potential.

Because cardiac muscle is myogenic, nervous stimulation is not necessary to elicit the heart beat. However, the heart rate is modulated by input from the autonomic nervous system. The sympathetic and parasympathetic systems innervate the SA node. Sympathetic stimulation causes an increase in heart rate or an increased number of beats/min. Norepinephrine, which stimulates Pj-adrenergic receptors, increases the rate of pacemaker depolarization by increasing the permeability to Na+ and Ca++ ions. If the heart beat is generated more rapidly, then the result is more beats per minute.

Parasympathetic stimulation causes a decrease in heart rate. Acetylcho-line, which stimulates muscarinic receptors, increases the permeability to potassium. Enhanced K+ ion efflux has a twofold effect. First, the cells become hyperpolarized and therefore the membrane potential is farther away from threshold. Second, the rate of pacemaker depolarization is decreased because the outward movement of K+ ions opposes the effect of the inward movement of Na+ and Ca++ ions. The result of these two effects of potassium efflux is that it takes longer for the SA node to reach threshold and generate an action potential. If the heart beat is generated more slowly, then fewer beats per minute are elicited.

From the SA node, the heart beat spreads rapidly throughout both atria by way of the gap junctions. As mentioned previously, the atria are stimulated to contract simultaneously. An interatrial conduction pathway extends from the SA node to the left atrium. Its function is to facilitate conduction of the impulse through the left atrium, creating the atrial syncytium (see Figure 13.3).

An internodal conduction pathway also extends from the SA node and transmits the impulse directly to the atrioventricular (AV) node. This node is located at the base of the right atrium near the interventricular septum, which is the wall of myocardium separating the two ventricles. Because the atria and ventricles are separated from each other by fibrous connective tissue, the electrical impulse cannot spread directly to the ventricles. Instead, the AV node serves as the only pathway through which the impulse can be transmitted to the ventricles. The speed of conduction through the AV node is slowed, resulting in a slight delay (0.1 sec). The cause of this AV nodal delay is partly due to the smaller fibers of the AV node. More importantly, however, fewer gap junctions exist between the cells of the node, which interne pathw;

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AV bundle

Bundle branches

Figure 13.3 Route of excitation and conduction in the heart. The heart beat is initiated in the sinoatrial (SA) node, or the pacemaker, in the right atrium of the heart. The electrical impulse is transmitted to the left atrium through the interatrial conduction pathway and to the atrioventricular (AV) node through the internodal pathway. From the AV node, the electrical impulse enters the ventricles and is conducted through the AV bundle, the left and right bundle branches, and, finally, the Purkinje fibers, which terminate on the true cardiac muscle cells of the ventricles.

AV bundle

Bundle branches

Figure 13.3 Route of excitation and conduction in the heart. The heart beat is initiated in the sinoatrial (SA) node, or the pacemaker, in the right atrium of the heart. The electrical impulse is transmitted to the left atrium through the interatrial conduction pathway and to the atrioventricular (AV) node through the internodal pathway. From the AV node, the electrical impulse enters the ventricles and is conducted through the AV bundle, the left and right bundle branches, and, finally, the Purkinje fibers, which terminate on the true cardiac muscle cells of the ventricles.

increases the resistance to current the flow. The physiological advantage of the AV nodal delay is that it allows atria to complete their contraction before ventricular contraction begins. This timing ensures proper filling of the ventricles prior to contraction.

From the AV node, the electrical impulse spreads through the AV bundle or the bundle of His. This portion of the conduction system penetrates the fibrous tissue separating the atria from the ventricles and enters the inter-ventricular septum where it divides into the left and right bundle branches. The bundle branches travel down the septum toward the apex of the heart and then reverse direction, traveling back toward the atria along the outer ventricle walls. This route of conduction of the impulse facilitates ejection of blood from the ventricles. If the impulse were to be conducted directly from the atria to the ventricles, the ventricular contraction would begin at the top of the chambers and proceed downward toward the apex. This would trap the blood at the bottom of the chambers. Instead, the wave of ventricular electrical stimulation and, therefore, contraction moves from the apex of the heart toward the top of the chambers where the semilunar valves are located and ejection takes place.

The final portion of the specialized conduction system consists of the Purkinje fibers that extend from the bundle branches. These fibers, which spread throughout the myocardium, terminate on the true cardiac muscle cells of the ventricles. The rate of conduction of the impulse through the Purkinje fibers is very rapid and results in the functional syncytium of the ventricles discussed earlier. The entire ventricular myocardium is stimulated almost simultaneously, which strengthens its pumping action. The increased rate of conduction (six times the rate of other ventricular muscle cells) is due in part to the large diameter of the Purkinje fibers. Furthermore, the gap junctions have a very high level of permeability, which decreases the resistance to current flow. It is estimated that Purkinje fibers conduct impulses at a velocity of 1.5 to 4.0 m/sec.

The action potential generated in the ventricular muscle is very different from that originating in the SA node. The resting membrane potential is not only stable; it is much more negative than that of the SA node. Second, the slope of the depolarization phase of the action potential is much steeper. Finally, there is a lengthy plateau phase of the action potential in which the muscle cells remain depolarized for approximately 300 msec. The physiological significance of this sustained depolarization is that it leads to sustained contraction (also about 300 msec), which facilitates ejection of blood. These disparities in the action potentials are explained by differences in ion channel activity in ventricular muscle compared to the SA node.

At rest, the permeability to K+ ions in ventricular muscle cells is significantly greater than that of Na+ ions. This condition results in a stable resting membrane potential that approaches the equilibrium potential for K+ of -90 mV (phase 4) (see Figure 13.2, panel B). Upon stimulation by an electrical impulse, the voltage-gated fast Na+ channels open, causing a marked increase in the permeability to Na+ ions and a rapid and profound depolarization of the membrane potential toward +30 mV (phase 0). These voltage-gated Na+ channels remain open very briefly and within 1 msec are inactivated. The resulting decrease in sodium permeability causes a small repolarization (phase 1). The ventricular muscle cells do not completely repo-larize immediately as do neurons and skeletal muscle cells. Instead, a plateau phase of the action potential (phase 2) occurs. During this phase, permeability to K+ ions decreases and permeability to Ca++ ions increases. Like the voltage-gated Na+ channels, the voltage-gated Ca++ channels are also activated by depolarization; however, they open much more slowly. The combination of decreased K+ ion efflux and increased Ca++ ion influx causes prolonged depolarization. Repolarization (phase 3) occurs when the Ca++ channels close and K+ channels open, allowing for rapid efflux of K+ ions and a return to the resting membrane potential.

As in neurons, cardiac muscle cells undergo an absolute or effective refractory period in which, at the peak of the action potential, the voltage-gated fast Na+ channels become inactivated and incapable of opening regardless of further stimulation. Therefore, the fast Na+ channels cannot reopen, Na+ ions cannot enter the cell, and another action potential cannot be generated. These channels do not return to their resting position and become capable of opening in sufficient numbers to generate a new action potential until the cardiac muscle cell has repolarized to approximately -70 mV. As a result, the absolute refractory period lasts almost as long as the duration of the associated contraction — about 250 msec. The physiological significance of this phenomenon is that it prevents the development of tetanus or spasm of the ventricular myocardium. By the time the cardiac muscle cell can be stimulated to generate another action potential, the contraction from the previous action potential is over. Therefore, tension from sequential action potentials cannot accumulate and become sustained. This is in contrast to skeletal muscle where tetanic contractions readily occur in order to produce maximal strength (Chapter 11). The pumping action of the heart, however, requires alternating contraction and relaxation so that the chambers can fill with blood. Sustained contraction or tetanus would preclude ventricular filling.

The effective refractory period is followed by a relative refractory period that lasts for the remaining 50 msec of the ventricular action potential. During this period, action potentials may be generated; however, the myocardium is more difficult than normal to excite.

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.